NEW YORK (GenomeWeb) – When he was first approached to head up the Japan Agency for Medical Research and Development (AMED), Makoto Suematsu was not interested.
For years, an agency in Japan that would be the equivalent of the US National Institutes of Health had been proposed only to eventually evaporate into the mist. Besides, as Dean of the Keio University School of Medicine, Suematsu enjoyed the research aspect of his career and he was not looking to become a government bureaucrat.
But, as he told GenomeWeb, "I have no chance to refuse the request by the Prime Minister," Shinzo Abe, and in spite of never actually having said yes to the offer, Suematsu now finds himself the founding president of AMED, tasked with the responsibility of changing the medical research funding process in Japan.
Officially launched in April, AMED represents a major step in Abe's ambitions to rejuvenate scientific research in Japan, a process that began about two years ago after he won re-election to lead the country. Armed with a $1.4 billion research and development budget, the agency's overarching missions, Suematsu said, are to fast-track medical R&D, improve the health of the Japanese people, and improve their quality of life.
"So in order to accomplish this … we really need to make [the] very heterogeneous system of funding in this country into one system," he said.
Historically, funding for research inJapanhas come from three separate ministries — the Ministry of Education, Culture, Sports, Science, and Technology; the Ministry of Health, Labor, and Welfare; and the Ministry of Economy, Trade, and Industry. The result is a funding system that researchers have complained about for years as being segmented and inefficient.
"These three ministries independently allocate research funding without any good coordination," Hidewaki Nakagawa of the Riken Center for Integrative Medical Sciences, Laboratory for Genome Sequencing Analysis told GenomeWeb in 2013.
Suematsu's job is to try to change that. During the next five years of his term, he will try to streamline research funding by consolidating some functions and simplifying the process. Further, he aims to change the research culture inJapanto spur on new discoveries and engender a collaborative environment, he said.
Suematsu faces daunting obstacles. For one thing, AMED's $1.4 billion R&D budget is a drop in the ocean. By comparison, the NIH's budget for the current fiscal year is about $30 billion.
Additionally, even with the creation of AMED, the economy, health, and education ministries maintain a significant say over the allocation of medical research funds, and disagreements over how the budget will be spent are bound to happen, Suematsu said.
"It is [a] very tough mission for me," he told GenomeWeb. "That means negotiations among the three different ministries."
Now with AMED added to the mix, it can also be argued that rather than streamlining the funding process, the creation of an additional agency may further muddy it. Suematsu said that given AMED is only a few months old, it remains a work in progress and many details about how its functions will be carried out remain to be determined.
He pointed out, though, that AMED is already taking real steps to improve the funding environment. Starting next April, the beginning of Japan's next fiscal year, for example, AMED will serve as the entry point for all researchers seeking funding. No longer will scientists have to wade through the various government agencies to figure out which one they need to contact if they have questions, Suematsu said.
Further, he noted that AMED has provided the research community a mechanism to share their concerns and recommendations. Much of his time going back to when he was first approached about heading the agency has been spent meeting with researchers to explain AMED to them and to collect comments from scientists about their funding experiences.
"And once I can receive all of these questions or plans for reforming the system, I can directly ask my excellent staff to change the rules in AMED. Such feedback never happened" before AMED's creation, he said.
Jumping right in
Two months after AMED's launch the agency initiated two projects, one called the Initiative on Rare and Undiagnosed Diseases (IRUD), directed at rare diseases using genomic technologies, and the other called the Drug Innovation and Screening Consortium (DISC), which is focused on new drug development.
With $5 million in funding for the current fiscal year, IRUD will leverage genomic technology to help diagnose patients suffering from medically undiagnosed conditions. It will include up to 1,000 children or adults who previously suffered from ailments that clinicians were unable to diagnose, and who will now be referred to 17 hospitals in Japan for diagnosis.
If diagnoses still cannot be made, the patients will then be referred to one of four institutions — the National Center for Child Health and Development; Keio University; Tohoku University; and Yokohama City University — where their blood samples will be sequenced in the hopes of identifying genetic aberrations that may underpin their diseases.
IRUD is expected to run for three more years beyond the current one, Suematsu said.
Meanwhile, DISC is aimed at collecting compound libraries from Japanese drug manufacturers and matching them with seed compounds from academia in the hopes of greasing the country's drug development pipeline.
Suematsu said that opening up their drug libraries is "very risky" for pharmaceutical companies, but that there is a "huge need" to do so for medical researchers in Japan conducting new drug research, as most Japanese universities don't have high-throughput screening systems such as those possessed by pharma firms.
In order to incentivize pharma to share their libraries, Suematsu said that AMED will provide some financial support to develop drug candidates resulting from the collaboration with universities. AMED also will cover the cost of analyses by universities using pharma's technologies.
To date, more than 20 Japanese pharmas have agreed to open up their libraries to academic researchers, and by year's end Suematsu said he anticipates several collaborations between university researchers and large and small pharmas to result from DISC.
The Japanese government is funding DISC with $8 million for the current fiscal year and the project is expected to run for at least five more years, Suematsu said.
Aside from simplifying the funding process, Suematsu told GenomeWeb that he also wants to change the research culture in Japan, from the coursework required in medical schools to how universities use government funding. In particular, he highlighted the need for data sharing.
Indeed, while the primary objective of IRUD is to develop diagnostics and to better manage and treat patients, he said that the project aims to address the unwillingness of researchers in Japan to let their colleagues view their data.
In rare and undiagnosed diseases, he said that Japan has a long history of research, as well as "excellent data … but there is no data sharing in [a] real-time manner with other countries."
Though various international efforts aimed at rare and undiagnosed diseases have been created in recent years, such as the International Rare Diseases Research Consortium, Japan has largely stood on the sidelines, according to Suematsu, even though individual scientists have actively pursued research in the area.
Japan is not unique in that respect, but some nations have also taken steps to increase the transparency of research data. For example, in the US the NIH codified data-sharing practices with the Genomic Data Sharing Policy, issued in 2008, in order to encourage researchers to share their data from genome-wide association studies that are supported by the institute.
Also, parts of the research community have taken it upon themselves to require the sharing of data. In genomics, the International Human Genome Sequence Consortium adopted the Bermuda Principles that mandate the rapid, automatic release of sequence assemblies greater than a kilobase, followed by the sharing of full, annotated sequences.
Suematsu said, however, that he has already seen push-back from Japanese researchers. "That is very difficult. I am concerned a bit," he said. Regardless, AMED may make the public sharing of data mandatory for researchers in order to receive public funding.
"Now, once the researcher can receive the budget from AMED, we will ask all researchers to submit the data for [a] clinical database for rare diseases," he said. "Otherwise, the database will be something like a silo."
According to Riken's Nakagawa, it's a change that's overdue. Genomic data, he said, should be shared at least among researchers in Japan, even if it isn't shared internationally. By creating a critical mass of data from the Japanese population, "we can construct an excellent database (genome and clinical information), which can be useful to establish precision medicine in Japan," he told GenomeWeb in an email this week.
Another practice that Suematsu hopes to change is the use by Japanese universities of what he called "indirect budgets." As he explained it, universities routinely take a sizeable share of funding received by researchers for their own purposes. For example, if a researcher receives a $1 million government grant, the university will skim off 30 percent — the percentage varies from university to university — leaving, in reality, $700,000 for the researcher for his work.
"It's a very unhappy situation," Suematsu said, adding that in discussions with researchers many identified "indirect budgets" as an especially onerous burden.
His goal, at least in the short term, is to make transparent how much each university takes from research grants for its "indirect budget," and by doing so, perhaps subtly influence universities to decrease the percentage they take, or even do away with the practice, out of fear that their researchers would leave for other institutions that take a lower share or none at all.
AMED has no way of directly forcing universities to make public their policies regarding "indirect budgets," but the education ministry does. "So in this case, I use the power of the Ministry of Education to ask [for] transparency from all the universities," he said.
The creation of AMED is part of a multi-armed initiative by Prime Minister Abe to revitalize Japan's economy. Dubbed Abenomics, the strategy has included investments into the country's scientific research in order to stimulate new medical discoveries, drugs, diagnostics, and devices, and return Japan to its role as a leader in scientific research. Since returning to office in late 2012 — Abe was also Japan's Prime Minister between 2006 and 2007 — Abe and his administration have poured billions of dollars into rebuilding the country's scientific infrastructure.
AMED was first floated as part of the administration's strategy a little more than two years ago. The response from the scientific community was tepid. Soon after the idea for AMED was announced, about 50 scientific societies in Japan signed an "Emergency Declaration" expressing their concerns about how AMED would allocate its budget. Specifically, the basic science research community feared that the new agency would funnel funds to applications-based projects at the expense of basic research.
"The basic researcher wants to keep their own budget, not [have it go to] applied science or medicine," Suematsu said.
As it turns out, though, most of the funding for basic research is provided through a mechanism called Grants-in-Aid for Scientific Research and remains out of the hands of AMED, at least for now.
As he met with basic researchers, Suematsu said that he also tried to allay their fears. While his background is primarily in medicine, Suematsu said that he has great respect for basic research, and, "I always emphasize the importance of basic science." Conversely, clinical research can lead to important discoveries in the basic sciences, so "a good [portion] of basic science funding is really necessary. This is one very important component of AMED," he said.
He added that NIH Director Francis Collins as well as UK health officials told him that basic research needs to be a main funding priority, and they suggested the proper ratio of funding for basic research, translational science, and clinical research is 5:3:2.
"This is a kind of golden ratio," Suematsu said, though AMED's own baseline level is about 40 percent of its budget for research into the basic sciences.
In genomics, AMED's plans for now remain modest. Even with the $5 million set aside for IRUD this fiscal year, Suematsu acknowledged that the agency's budget for genomic research is "very limited," though he added that next year, "we will start the budget for clinical genetics."
He highlighted two areas in particular as priorities for genomics funding, a continued emphasis on rare and undiagnosed diseases and cancer. Separate from AMED, Japan has made developing new cancer drugs a key priority, Suematsu said, "and we will stimulate these activities and open up the opportunity to use … cancer genomic panels all over Japan."
He added that two to three years will be necessary to establish an infrastructure for such work.
As part of AMED's clinical genetics efforts, Suematsu said that rather than providing funding to researchers "at random," his vision is to create four or five core facilities that will perform clinical genomic analysis.
Such an approach would be a more efficient use of funding, he said. Otherwise, if just a few universities wanted to buy a next-generation sequencer, for example, a large chunk of AMED's budget would be rapidly depleted.
Additionally, it would encourage collaboration between academia and industry. Industry, Suematsu said, would be expected to provide some of the money to establish the core facilities, and in return they would potentially have the commercialization rights to technologies resulting from the collaborations.
He also noted that by creating a number of core facilities — as opposed to one central clinical genomics data site — any jealousies among the different universities in Japan would be mitigated.
Suematsu acknowledged that Japan has a lot of catching up to do in the genomics space, and in whole-genome analysis, especially, "we need a different infrastructure." He explained that in addition to a lack of funding for genomic medicine in Japan, technologies including next-generation sequencing instruments that were placed in institutions such as hospitals have not been used for clinical purposes, or when clinical sequencing was conducted, the results too often were not relayed back to patients.
"In other words, coordination between [the Ministry of Health and the Ministry of Education] to hybridize the basic genome research and clinical application appeared to … fail for many years," Suematsu said.
One step that AMED has taken to allow researchers more flexibility in using government funding is to change a rule that had barred the multipurpose use of funds. Japanese regulations had prohibited, for example, an NGS instrument that had been bought for one project to be used for another project, Suematsu said. But after negotiations with the different ministries, AMED has reformed those rules.
"Needless to say, [the] regulation of clinical use of NGS is the next problem to be tackled," he said, adding that AMED and the Pharmaceuticals and Medical Devices Agency of Japan — that country's equivalent of the US Food and Drug Administration — last week formed an alliance that is expected to accelerate clinical sequencing in Japan.
As Japan tries to jump start its genomics research, AMED will play a crucial role, said Nakagawa, who in addition to his position at Riken is now a program officer for genomic medicine and biobanking at AMED.
Promoting genomic medicine "is one of the most important missions of AMED," he said. "In Japan there are a lot of hurdles or challenges preventing genomic medicine," and creating a Japanese genomic database "and sharing this with domestic institutes and other agents abroad are also important issues."
Another step Suematsu hopes to implement is a program to foster young genomics investigators and to tie in basic research with clinical applications. For the past two decades, such an approach has been virtually non-existent, he said.
"We really need to understand what's going on in the patient … and we really need fostering of the clinical [geneticist] who understands both pediatrics and internal medicine," Suematsu said, adding that the Japanese medical education, in large part, ignores clinical genetics.
"I believe that reforming medical education to be adapted to modern genome medicine is essential," he said. One possibility being explored with the Ministry of Education is making clinical genetics courses mandatory in medical school.
As Suematsu and his staff of nearly 400 continue to get AMED off the ground, he acknowledged that it will be important to get things right quickly in order to ensure the future of the agency.
Nakagawa, for one, is taking a hopeful if cautious view of AMED. He said that AMED's $1.4 billion R&D budget is "obviously … not enough" to accomplish all that needs to get done. He also said that in order to effect real change, AMED will eventually need to be in charge of the medical research budget instead of having it divvied up among so many different agencies.
"Sectionalism is very common in [Japanese funding], and we need a long discussion to change and overcome the sectionalism," he said. "Budget drafting and research planning is still performed mainly by [the] ministries, and their opinions are strong to determine the budgets.
"I hope in a [few years] this situation will be changed and AMED can have some initiative to draft the budget," Nakagawa continued. "But this change is likely to be slow. This may be Japanese style and it would take a long time to make a big change in Japan."